GUARDIAN (NCT04884802) Sub-study, Phenylephrine v. Norepinephrine
Study Details
Study Description
Brief Summary
Some patients participating in the underlying GUARDIAN trial (NCT04884802) will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Patients participating in the underlying GUARDIAN trial (NCT04884802) will be randomized to:
- norepinephrine or phenylephrine infusion to maintain intraoperative MAP ≥85 mmHg, delayed resumption of chronic antihypertensive medications, and a target ward systolic pressure of at least 110 mmHg (tight pressure management); or, 2) routine intraoperative blood pressure management and prompt resumption of chronic antihypertensive medications (routine pressure management). Patients participating in this sub-study will be additionally randomized to norepinephrine or phenylephrine infusion to maintain the designated target intraoperative mean arterial pressure.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Tight Pressure Management with phenylephrine Pressure maintenance with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial. |
Drug: Phenylephrine
Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
|
| Active Comparator: Tight Pressure Management with norepinephrine Pressure maintenance with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial. |
Drug: Norepinephrine
Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
|
| Active Comparator: Routine Pressure Management with phenylephrine Pressure maintenance with phenylephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial |
Drug: Phenylephrine
Phenylephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
|
| Active Comparator: Routine Pressure Management with norepinephrine Pressure maintenance with norepinephrine infusion at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial. |
Drug: Norepinephrine
Norepinephrine will be infused at a rate sufficient to maintain the intraoperative MAP designated in the underlying GUARDIAN trial.
|
Outcome Measures
Primary Outcome Measures
- Composite of major perfusion-related complications [30 days after major non-cardiac surgery]
Composite of major perfusion-related complications (Myocardial injury, stroke, non-fatal cardiac arrest, stage 2-3 acute kidney injury, sepsis, and death
Secondary Outcome Measures
- Postoperative delirium [4 Postoperative hospital days]
Three dimensional Confusion Assessment Method (3D CAM)
Eligibility Criteria
Criteria
Inclusion Criteria:
-
At least 45 years old;
-
Scheduled for major noncardiac surgery expected to last at least 2 hours;
-
Having general anesthesia, neuraxial anesthesia, or the combination;
-
Expected to require at least overnight hospitalization (planned ICU admission is acceptable);
-
Are designated ASA physical status 2-4 (ranging from mild systemic disease through severe systemic disease that is a constant threat to life);
-
Chronically taking at least one anti-hypertensive medication;
-
Expected to have direct intraoperative blood pressure monitoring with an arterial catheter;
-
Cared for by clinicians willing to follow the GUARDIAN protocol;
-
Subject to at least one of the following risk factors:
-
Age >65 years;
-
History of peripheral arterial surgery;
-
History of coronary artery disease;
-
History of stroke or transient ischemic attack;
-
Serum creatinine >175 µmol/L (>2.0 mg/dl);
-
Diabetes requiring medication;
-
Current smoking or 15 pack-year history of smoking tobacco;
-
Scheduled for major vascular surgery;
-
Body mass index ≥35 kg/m2;
-
Preoperative high-sensitivity troponin T >14 ng/L or troponin I equivalent, defined as ≥15 ng/L (Abbott assay),77 19 ng/L (Siemens assay, [Borges, unpublished]), or 25% of the 99% percentile for other assays;
-
B-type natriuretic protein (BNP) >80 ng/L or N-terminal B-type natriuretic protein (NT-ProBNP) >200 ng/L.78,79
Exclusion Criteria:
-
Are scheduled for carotid artery surgery;
-
Are scheduled for intracranial surgery;
-
Are scheduled for partial or complete nephrectomy;
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Are scheduled for pheochromocytoma surgery;
-
Are scheduled for liver or kidney transplantation;
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Require preoperative intravenous vasoactive medications;
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Have a condition that precludes routine or tight blood pressure management such as surgeon request for relative hypotension;
-
Require beach-chair positioning;
-
Have a documented history of dementia;
-
Have language, vision, or hearing impairments that may compromise cognitive assessments;
-
Have contraindications to norepinephrine or phenylephrine per clinician judgement;
-
Have previously participated in the GUARDIAN trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
Sponsors and Collaborators
- The Cleveland Clinic
Investigators
- Study Chair: Daniel I Sessler, MD, The Cleveland Clinic
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GUARDIAN, Vasopressor